Background: Liver transplant (LT) remains the best curative standard for HCC within Milan criteria (Milan). Nonsurgical locoregional treatments, including TACE and ablation, offer a bridge to surgical management and attempt to downstage or maintain patients (pts) within Milan pending liver transplant and donor organ availability. We investigated clinical factors that predict successful downstaging of HCC and liver transplant. Methods: In this single-institutional retrospective analysis, pts with early-intermediate stage HCC within Milan (control) vs beyond Milan were evaluated for clinical outcome. Clinical factors including treatment and response, demographics, TACE distribution (number of treatments, timing, and response), and status of liver transplantation (timing and if received) were correlated to overall survival (OS). OS was calculated using the Kaplan-Meier method. Results: HCC pts (n = 343) considered for LT or downstage to LT were included in the study: 75% male, 13% African American, 55% Caucasian, and 14% Asian. 12% of pts had HBV, 53% had HCV, 2% had both HBV and HCV. 221 pts were diagnosed within Milan vs 122 beyond Milan, in which 36% (n = 44) were still within UCSF criteria (UCSF). 43% of those diagnosed within Milan ultimately received LT vs 16% of those diagnosed beyond Milan. 49% of pts (n = 60) initially beyond Milan were downstaged to within Milan, via TACE, wherein 27% received LT; this group accounted for 13% all LT. However, in the subset of pts beyond Milan but within UCSF, 68% were downstaged to within Milan, wherein 40% received LT. In pts initially within Milan, 21% (n = 47) progressed beyond Milan, but 40% of this subset was downstaged back to within Milan. Pts both within and beyond Milan had a median of 2 TACE procedures. Differences in the rates of LT relative to the number of TACE were significant (p = 0.022) for pts initially within Milan; for < / = 2 TACE, 54% had LT; for > 2 TACE, 26% had LT. Similar comparison was nonsignificant for pts initially beyond Milan (p = 0.95); rates of LT for < / = 2 TACE and > 2 TACE were 17% and 16% respectively. Median OS for non-LT recipients was 5 years vs not reached for LT recipients ( > 70% alive at 8 years, p < 0.001). Pts initially beyond Milan but within UCSF criteria had similar OS vs those initially within Milan (both 75% at 4 years), but OS was worse (50% at 4 years) for those beyond UCSF (p = 0.024). Conclusions: Liver transplantation significantly increased OS in early-intermediate stage HCC. Increased number of TACE procedures was associated with decreased likelihood of ultimate LT in pts initially diagnosed within Milan, particularly when they had > 2 TACE. Pts initially beyond Milan but within UCSF criteria had similar OS vs those initially within Milan; this former subset had a good chance of being downstaged to Milan and ultimately receive LT. Additional clinical factors that predict successful downstaging of HCC and LT are being investigated.